This application is a filing under 35 USC 371 of PCT/FR99/00860 filed Apr. 13, 1999.
The present invention relates to an ionic aqueous composition containing levomenthol.
The nasal cavity contains sensitive receptors which are stimulated by the passage of air. When external modifications intervene, such as infestation by rhinovirus, variations in temperature or in atmospheric pressure for example, the mucous membranes of the nasal cavity react and get congested, and this creates a feeling of a blocked nose. This benign affectation, which is commonly called the cold, normally gets better spontaneously but sometimes does lead, over several days, to a sensation of respiratory discomfort and a secretory malfunctioning of the nasal mucous membranes, which can give rise to a significant discomfort under numerous circumstances such as at work or for sleeping suitably, for example.
Several treatments are currently proposed. Via the general route or via the local route, these are medicaments which have a vasoconstrictory action. Their long term use can however cause local or general side-effects which are linked to their pharmacological action, which can be serious, such as an atrophy of the nasal mucous membranes or cardiovascular or prostate troubles. Another treatment consists in the local administration of essential oils and/or of terpenic aromatic derivatives. Their local decongestant or antiseptic action, often claimed, is not however scientifically proved, and their use, alone or in combination, can prove to be dangerous for health by risking causing local irritations with the essential oils, or central nervous system troubles, such as convulsions in the infant with camphor, for example. The risk is increased when these preparations contain alcohol, even in low proportions, or antiseptic substances, used for preventing microbial contamination but which can be irritants to the nasal mucous membranes. Infants, young children or elderly subjects are more particularly exposed to all these risks.
Natural menthol is a secondary alcohol of essence of mint which contains levomenthol but also menthone. Synthetic menthol or dl menthol is an alcohol which is obtained by various synthetic methods, but 1-menthol or levomenthol, which is the most active isomer for aromatisation, can also be isolated or synthesised (cf. Codex 1965-DORVAULT L""OFFICINE, Vigot, 23rd ed. p.1055-MARTINDALE, THE EXTRA PHAMARCOPEIA, The Pharmaceutical Press, 30th ed. p. 1386).
It has already been proposed to use menthol, even levomenthol in compositions which are intended for decongesting the nasal mucous membranes.
However, menthol being known for its low solubility in aqueous solution, various tricks are used for using it at concentrations higher than its limit of solubility in water, either by incorporating it in emulsions, or by introducing various organic products such as an oil or an alcohol to improve its dispersion.
The present invention results from a reverse process since the inventor has now discovered that it was possible to prepare particularly effective compositions by using levomenthol at a concentration which does not go over the limit of solubility of this latter compound, with the proviso of dissolving it in a sufficiently ionic aqueous medium, and more specifically a medium which is at least isotonic, and preferably even quite clearly hypertonic.
It will be recalled that in physiology, the term  less than  less than isotonic greater than  greater than  is qualified as as solution which exerts an osmotic pressure which is equal to that of normal blood plasma, e.g. physiological NaCl solute at 9 g per liter. A hypertonic solution means a solution which exerts an osmotic pressure which is greater than that of normal bold plasma (example: NaCl solute the concentration of which is greater than 9 g per liter). It is in this sense that it is necessary to understand the terms  less than  less than isotonic greater than  greater than  or  less than  less than hypertonic greater than  greater than .
As it emerges from the following description, insofar as solutions are covered here which optionally contain ions other than those which constitute sodium chloride, their osmolarity will be referred to in order to define the osmotic behaviour of the ionic solutions of the invention.
The osmolarity of a solution is designated as the concentration of the osmotically active particles, such as ions, in this solution. In physiology, solutions having an osmolarity equal to that of blood plasma are commonly called  less than  less than iso-osmotic greater than  greater than  solutions. Those solutions having a higher osmolarity are called  less than  less than hyperosmotic greater than  greater than  solutions.
More specifically, the invention relates to a novel composition in the form of an aqueous solution, notably intended for relieving the sensation of respiratory discomport and/or for promoting the natural regeneration of the mucous membranes of the nasal cavity. This solution is essentially constituted of a levomenthol solution in an aqueous ionic solution having an osmolarity at least equal to that of an aqueous solution of sodium chloride at 9 g/l and in which the levomenthol is dissolved, said aqueous ionic solution being selected from the group constituted of pure or diluted sea water and aqueous sodium chloride solutions optionally further containing at least one salt naturally contained in sea water, the levomenthol being found at a concentration between 10 and 250 mg/l.
This composition has the double advantage of providing:
1) In the first place, an action of washing the nasal mucous membranes congested by a hypertonic or hyperosmotic ionic aqueous solution, or at least an isotonic or iso-osmotic solution. This washing action removes the mucus present on the congested mucous membranes and causes an osmotic effect, and this facilitates the natural regeneration of the mucous membranes of the nasal cavity. This aqueous ionic solution can be either pure or diluted sea water, or it can be water containing sodium chloride and, if need be, other salts naturally contained in sea water. The concentration of sodium chloride, of the solution selected, is preferably equal to or greater than 9 grams per liter, a concentration which is called isotonic with blood or tears.
2) In second place, and additionally, an action on the heat-receptors or cold receptors of the mucous membranes of the nasal cavity. This action is obtained by the use of levomenthol, the only isomer of menthol being active on the heat-receptors or cold receptors, of the mucous membranes of the nasal cavity. Levomenthol acts on the flow of calcium ions through the cell membranes of these receptors. A refreshing effect is thus instantaneously felt and procures a sensation of ease of breathing which enables the sensation of respiratory discomfort due to the nasal congestion to be decreased, in anticipation of a natural regeneration of the mucous membranes of the nasal cavity and without the use of other substances or medicaments which might be dangerous.